Real-time monitoring of proton exchange membrane fuel cell stack failure

Uneven pressure drops in a 75-cell 9.5-kWe proton exchange membrane fuel cell stack with a U-shaped flow configuration have been shown to cause localised flooding. Condensed water then leads to localised cell heating, resulting in reduced membrane durability. Upon purging of the anode manifold, the resulting mechanical strain on the membrane can lead to the formation of a pin-hole/membrane crack and a rapid decrease in open circuit voltage due to gas crossover. This failure has the potential to cascade to neighbouring cells due to the bipolar plate coupling and the current density heterogeneities arising from the pin-hole/membrane crack. Reintroduction of hydrogen after failure results in cell voltage loss propagating from the pin-hole/membrane crack location due to reactant crossover from the anode to the cathode, given that the anode pressure is higher than the cathode pressure. Through these observations, it is recommended that purging is avoided when the onset of flooding is observed to prevent irreparable damage to the stack

Molecular architecture of potassium chloride co-transporter KCC2

KCC2 is a neuron specific K+-Cl− co-transporter that controls neuronal chloride homeostasis, and is critically involved in many neurological diseases including brain trauma, epilepsies, autism and schizophrenia. Despite significant accumulating data on the biology and electrophysiological properties of KCC2, structure-function relationships remain poorly understood. Here we used calixarene detergent to solubilize and purify wild-type non-aggregated and homogenous KCC2. Specific binding of inhibitor compound VU0463271 was demonstrated using surface plasmon resonance (SPR). Mass spectrometry revealed glycosylations and phosphorylations as expected from functional KCC2. We show by electron microscopy (EM) that KCC2 exists as monomers and dimers in solution. Monomers are organized into “head” and “core” domains connected by a flexible “linker”. Dimers are asymmetrical and display a bent “S-shape” architecture made of four distinct domains and a flexible dimerization interface. Chemical crosslinking in reducing conditions shows that disulfide bridges are involved in KCC2 dimerization. Moreover, we show that adding a tag to the C-terminus is detrimental to KCC2 function. We postulate that the conserved KCC2 C-ter may be at the interface of dimerization. Taken together, our findings highlight the flexible multi-domain structure of KCC2 with variable anchoring points at the dimerization interface and an important C-ter extremity providing the first in-depth functional architecture of KCC2

Direct activation of KCC2 arrests benzodiazepine refractory status epilepticus and limits the subsequent neuronal injury in mice

Hyperpolarizing GABAAR currents, the unitary events that underlie synaptic inhibition, are dependent upon efficient Cl− extrusion, a process that is facilitated by the neuronal specific K+/Cl− co-transporter KCC2. Its activity is also a determinant of the anticonvulsant efficacy of the canonical GABAAR-positive allosteric: benzodiazepines (BDZs). Compromised KCC2 activity is implicated in the pathophysiology of status epilepticus (SE), a medical emergency that rapidly becomes refractory to BDZ (BDZ-RSE). Here, we have identified small molecules that directly bind to and activate KCC2, which leads to reduced neuronal Cl− accumulation and excitability. KCC2 activation does not induce any overt effects on behavior but prevents the development of and terminates ongoing BDZ-RSE. In addition, KCC2 activation reduces neuronal cell death following BDZ-RSE. Collectively, these findings demonstrate that KCC2 activation is a promising strategy to terminate BDZ-resistant seizures and limit the associated neuronal injury

Mice lacking the Cβ subunit of PKA are resistant to angiotensin II-induced cardiac hypertrophy and dysfunction

<p>Abstract</p> <p>Background</p> <p>PKA is a ubiquitous, multi-subunit cellular kinase that regulates a number of different physiological responses in response to cAMP, including metabolism, cell division, and cardiac function. Numerous studies have implicated altered PKA signaling in cardiac dysfunction. Recently, it has been shown that mice lacking the catalytic β subunit of PKA (PKA Cβ) are protected from age-related problems such as weight gain and enlarged livers, and we hypothesized that these mice might also be resistant to cardiomyopathy.</p> <p>Findings</p> <p>Angiotensin II (ang II) induced hypertension in both PKA Cβ null mice and their WT littermates. However, PKA Cβ null mice were resistant to a number of ang II-induced, cardiopathological effects observed in the WT mice, including hypertrophy, decreased diastolic performance, and enlarged left atria.</p> <p>Conclusion</p> <p>The Cβ subunit of PKA plays an important role in angiotensin-induced cardiac dysfunction. The Cβ null mouse highlights the potential of the PKA Cβ subunit as a pharmaceutical target for hypertrophic cardiac disease.</p

ADARRI:a novel method to detect spurious R-peaks in the electrocardiogram for heart rate variability analysis in the intensive care unit

We developed a simple and fully automated method for detecting artifacts in the R-R interval (RRI) time series of the ECG that is tailored to the intensive care unit (ICU) setting. From ECG recordings of 50 adult ICU-subjects we selected 60 epochs with valid R-peak detections and 60 epochs containing artifacts leading to missed or false positive R-peak detections. Next, we calculated the absolute value of the difference between two adjacent RRIs (adRRI), and obtained the empirical probability distributions of adRRI values for valid R-peaks and artifacts. From these, we calculated an optimal threshold for separating adRRI values arising from artifact versus non-artefactual data. We compared the performance of our method with the methods of Berntson and Clifford on the same data. We identified 257,458 R-peak detections, of which 235,644 (91.5%) were true detections and 21,814 (8.5%) arose from artifacts. Our method showed superior performance for detecting artifacts with sensitivity 100%, specificity 99%, precision 99%, positive likelihood ratio of 100 and negative likelihood ratio <0.001 compared to Berntson’s and Clifford’s method with a sensitivity, specificity, precision and positive and negative likelihood ratio of 99%, 78%, 82%, 4.5, 0.013 for Berntson’s method and 55%, 98%, 96%, 27.5, 0.460 for Clifford’s method, respectively. A novel algorithm using a patient-independent threshold derived from the distribution of adRRI values in ICU ECG data identifies artifacts accurately, and outperforms two other methods in common use. Furthermore, the threshold was calculated based on real data from critically ill patients and the algorithm is easy to implement

Beaked whales respond to simulated and actual navy sonar

This article is distributed under the terms of the Creative Commons Public Domain declaration. The definitive version was published in PLoS One 6 (2011): e17009, doi:10.1371/journal.pone.0017009.Beaked whales have mass stranded during some naval sonar exercises, but the cause is unknown. They are difficult to sight but can reliably be detected by listening for echolocation clicks produced during deep foraging dives. Listening for these clicks, we documented Blainville's beaked whales, Mesoplodon densirostris, in a naval underwater range where sonars are in regular use near Andros Island, Bahamas. An array of bottom-mounted hydrophones can detect beaked whales when they click anywhere within the range. We used two complementary methods to investigate behavioral responses of beaked whales to sonar: an opportunistic approach that monitored whale responses to multi-day naval exercises involving tactical mid-frequency sonars, and an experimental approach using playbacks of simulated sonar and control sounds to whales tagged with a device that records sound, movement, and orientation. Here we show that in both exposure conditions beaked whales stopped echolocating during deep foraging dives and moved away. During actual sonar exercises, beaked whales were primarily detected near the periphery of the range, on average 16 km away from the sonar transmissions. Once the exercise stopped, beaked whales gradually filled in the center of the range over 2–3 days. A satellite tagged whale moved outside the range during an exercise, returning over 2–3 days post-exercise. The experimental approach used tags to measure acoustic exposure and behavioral reactions of beaked whales to one controlled exposure each of simulated military sonar, killer whale calls, and band-limited noise. The beaked whales reacted to these three sound playbacks at sound pressure levels below 142 dB re 1 µPa by stopping echolocation followed by unusually long and slow ascents from their foraging dives. The combined results indicate similar disruption of foraging behavior and avoidance by beaked whales in the two different contexts, at exposures well below those used by regulators to define disturbance.The research reported here was financially supported by the United States (U.S.) Office of Naval Research (www.onr.navy.mil) Grants N00014-07-10988, N00014-07-11023, N00014-08-10990; the U.S. Strategic Environmental Research and Development Program (www.serdp.org) Grant SI-1539, the Environmental Readiness Division of the U.S. Navy (http://www.navy.mil/local/n45/), the U.S. Chief of Naval Operations Submarine Warfare Division (Undersea Surveillance), the U.S. National Oceanic and Atmospheric Administration (National Marine Fisheries Service, Office of Science and Technology) (http://www.st.nmfs.noaa.gov/), U.S. National Oceanic and Atmospheric Administration Ocean Acoustics Program (http://www.nmfs.noaa.gov/pr/acoustics/), and the Joint Industry Program on Sound and Marine Life of the International Association of Oil and Gas Producers (www.soundandmarinelife.org)

Role of Muscarinic Acetylcholine Receptors in Serial Feature-Positive Discrimination Task during Eyeblink Conditioning in Mice.

We investigated the role of muscarinic acetylcholine receptors (mAChRs) in eyeblink serial feature-positive discrimination learning in mice using the mAChR antagonist. A 2-s light cue was delivered 5 or 6 s before the presentation of a 350-ms tone paired with a 100-ms periorbital electrical shock (cued trial) but not before the tone-alone presentation (non-cued trial). Mice received 30 cued and 30 non-cued trials each day in a random order. We found that saline-injected control mice were successfully discriminating between cued and non-cued trials within a few days of conditioning. The mice responded more frequently to the tone in cued trials than in non-cued trials. Analysis of conditioned response (CR) dynamics revealed that the CR onset latency was shorter in cued trials than in non-cued trials, despite the CR peak amplitude not differing significantly between the two conditions. In contrast, scopolamine-injected mice developed an equal number of CRs with similar temporal patterns irrespective of the presence of the cue during the 7 days of conditioning, indicating in a failure to acquire conditional discrimination. In addition, the scopolamine administration to the control mice after they had successfully acquired discrimination did not impair the conditional discrimination and expression of pre-acquired CR. These results suggest that mAChRs may play a pivotal role in memory formation in the conditional brain state associated with the feature cue; however they are unlikely to be involved in the development of discrimination after conditional memory had formed in the serial feature-positive discrimination task during eyeblink conditioning

The Correlation between Running Economy and Maximal Oxygen Uptake: Cross-Sectional and Longitudinal Relationships in Highly Trained Distance Runners

A positive relationship between running economy and maximal oxygen uptake (V̇O2max) has been postulated in trained athletes, but previous evidence is equivocal and could have been confounded by statistical artefacts. Whether this relationship is preserved in response to running training (changes in running economy and V̇O2max) has yet to be explored. This study examined the relationships of (i) running economy and V̇O2max between runners, and (ii) the changes in running economy and V̇O2max that occur within runners in response to habitual training. 168 trained distance runners (males, n = 98, V̇O2max 73.0 ± 6.3 mLkg-1min-1; females, n = 70, V̇O2max 65.2 ± 5.9 mL kg-1min-1) performed a discontinuous submaximal running test to determine running economy (kcalkm-1). A continuous incre-mental treadmill running test to volitional exhaustion was used to determine V̇O2max 54 par-ticipants (males, n = 27; females, n = 27) also completed at least one follow up assessment. Partial correlation analysis revealed small positive relationships between running economy and V̇O2max (males r = 0.26, females r = 0.25; P&lt;0.006), in addition to moderate positive re-lationships between the changes in running economy and V̇O2max in response to habitual training (r = 0.35; P&lt;0.001). In conclusion, the current investigation demonstrates that only a small to moderate relationship exists between running economy and V̇O2max in highly trained distance runners. With&gt;85 % of the variance in these parameters unexplained by this relationship, these findings reaffirm that running economy and V̇O2max are primarily determined independently

C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older.

Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (-174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95% CI = 1.03-2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation

Modeling Boundary Vector Cell Firing Given Optic Flow as a Cue

Boundary vector cells in entorhinal cortex fire when a rat is in locations at a specific distance from walls of an environment. This firing may originate from memory of the barrier location combined with path integration, or the firing may depend upon the apparent visual input image stream. The modeling work presented here investigates the role of optic flow, the apparent change of patterns of light on the retina, as input for boundary vector cell firing. Analytical spherical flow is used by a template model to segment walls from the ground, to estimate self-motion and the distance and allocentric direction of walls, and to detect drop-offs. Distance estimates of walls in an empty circular or rectangular box have a mean error of less than or equal to two centimeters. Integrating these estimates into a visually driven boundary vector cell model leads to the firing patterns characteristic for boundary vector cells. This suggests that optic flow can influence the firing of boundary vector cells